Schizophrenia & Animal Research

How does animal research help us understand a complex human mental illness such as schizophrenia? After all rats and mice are obviously very different from humans, so how can their simpler brains help us understand the same kind of complex symptoms as humans? In this review, the authors summarize the importance of animal models for research on schizophrenia.

Ethics

Just like in human research, animal research is governed by local animal rights ethics committees that monitor ethical use of animals in research. Scientists are responsible for explaining exactly why animals are needed, what they are used for and how the results benefit human clinical practice. Strict controls apply – for example the scientist is supposed to use as few animals as possible, use the best possible methods and pay special attention to minimizing pain or discomfort in the animals.

Creating Symptoms for Medication Development

Overall, it is very difficult to completely reproduce a disease as complex as schizophrenia in an animal. Instead, other approaches are used. For example, animals are used to study the effect of new treatments. Movement in rats (locomotor) is often induced by drugs (eg. amphetamine) which results in hyperactivity which is then used to model the positive symptoms of schizophrenia. After the hyperactivity is induced, the rat might be given a medication like Haldol which reduces this hyperactivity by blocking certain (dopamine) receptors in the brain. This then helps understand how certain anti psychotic medications work and how new medications can be developed. In fact, it was only after these early studies in rats that human researchers were able to figure out that psychosis in humans is partly due to increases in certain chemical in the brain (eg. dopamine) – which then allowed medications to be developed to treat this chemical imbalance.

There is another way that selected symptoms of schizophrenia are mimicked in animals. Prepulse inhibition (PPI) is widely used to look at sensory information processing problems (sensorimotor gating) that underlie some symptoms of schizophrenia. This PPI is a shielding mechanism against sensory information overload. In rats, treatment with certain dopaminergic drugs causes a disruption of PPI similar to that seen in those who have schizophrenia. This information has then been used to test various medications and also look at the effect of different interventions that can influence this PPI.

Negative symptoms of schizophrenia have also been modeled in rats. For instance, social withdrawal has been relatively easy to measure in animals such as rats and monkeys by treating them certain medications (eg. phencyclidine) and then noticing a syndrome of stereotyped behaviour and reduced social interaction similar to schizophrenia. Different memory tests can then be used to look at thinking changes in these experimentally treated animals, which helps us understand the ways that thinking changes in schizophrenia and ways to treat it.
Genes

Schizophrenia clearly has a strong genetic or family basis. Animal research that looks at genetically modified mice models is a popular way to understand the role of genes in schizophrenia. For example, “transgenic mice” have had genes added whereas “knockout mice” have genes removed or inactivated. These types of mice have played important roles in helping us to learn about the function of the gene on the brain.

Conclusions
Overall researchers recognize that the exact expression of behaviors differ between humans and experimental animals. Yet, they have recognize that re-creating similarities in the underlying biological mechanisms that are involved in particular behaviors can help. Studies that would be very difficult to carry out in humans, both from a technical and an ethical point of view can be done with animal models which have proved to be important tools for studying the symptoms, development and treatment of schizophrenia.